An Explicative Review on the Progress of Quinazoline Scaffold as Bioactive Agents in the Past Decade.

In the last decade, quinazoline was one of the most explored scaffolds by researchers around the globe in medicinal chemistry. Its unique structural features provide a wide range of substitutions on nitrogen and carbonyl groups. In the current situation of COVID-19, hydroxychloroquine an antimalarial drug of the quinoline category was used for the treatment of severe infections. Various substitution patterns, hybrids, and conjugates of quinazoline have been developed and studied for various pharmacological activities like anticancer, anti-inflammatory, antimalarial, antitubercular, etc. The scaffold can be considered as a potential molecule for various pharmacological activities especially as antimicrobial and antihypertensive. The current review aims to study, physicochemical properties, chemistry, and pharmacological profile of quinazoline.

Discovery of Zafirlukast as a novel SARS-CoV-2 helicase inhibitor using in silico modelling and a FRET-based assay.

The coronavirus helicase is an essential enzyme required for viral replication/transcription pathways. Structural studies revealed a sulphate moiety that interacts with key residues within the nucleotide-binding site of the helicase. Compounds with a sulphoxide or a sulphone moiety could interfere with these interactions and consequently inhibit the enzyme. The molecular operating environment (MOE) was used to dock 189 sulphoxide and sulphone-containing FDA-approved compounds to the nucleotide-binding site. Zafirlukast, a leukotriene receptor antagonist used to treat chronic asthma, achieved the lowest docking score at -8.75 kcals/mol. The inhibitory effect of the compounds on the SARS-CoV-2 helicase dsDNA unwinding activity was tested by a FRET-based assay. Zafirlukast was the only compound to inhibit the enzyme (IC50 = 16.3 µM). The treatment of Vero E6 cells with 25 µM zafirlukast prior to SARS-CoV-2 infection decreased the cytopathic effects of SARS-CoV-2 significantly. These results suggest that zafirlukast alleviates SARS-CoV-2 pathogenicity by inhibiting the viral helicase and impairing the viral replication/transcription pathway. Zafirlukast could be clinically developed as a new antiviral treatment for SARS-CoV-2 and other coronavirus diseases. This discovery is based on molecular modelling, in vitro inhibition of the SARS-CoV helicase activity and cell-based SARS-CoV-2 viral replication.

A comprehensive review on the biological interest of quinoline and its derivatives.

Amongst heterocyclic compounds, quinoline is an advantaged scaffold that appears as a significant assembly motif for the development of new drug entities. Quinoline and its derivatives tested with diverse biological activity constitute an important class of compounds for new drug development. Therefore, many scientific communities have developed these compounds as intent structure and evaluated their biological activities. The present, review provides brief natural sources of quinoline and including a new extent of quinoline-based marketed drugs. This review also confers information about the biological activities of quinoline derivatives such as antibacterial, antifungal, antimycobacterial, antiviral, anti-protozoal, antimalarial, anticancer, cardiovascular, CNS effects, antioxidant, anticonvulsant, analgesic, anti-inflammatory, anthelmintic and miscellaneous activities.